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About me

Dr Giovanna Zinzalla, Forskare/junior PI in Chemical Biology

E-mail: giovanna.zinzalla@ki.se

Phone: +46 (0)76 555 1009

AREAS OF EXPERTISE

Organic and Medicinal Chemistry, Biochemistry, Structural Biology, Biochemical and Biophysical Assays, Structure-Based Molecular Design, Protein-Protein Interactions, Drug Discovery, Cancer Research.

LATEST PUBLICATIONS: 

For the up-to-date publication list (ie, including Early View articles) Click on the ResearchGate link below for Links,  or paste into your internet browser:  https://www.researchgate.net/profile/Giovanna_Zinzalla

BIOGRAPHY

Dr. Zinzalla obtained her first class honors Laurea in Chemistry (equivalent to MChem) from the University of Milan and carried out her PhD studies with Prof. Stefano Maiorana and Dr Clara Baldoli also at the University of Milan. Her research focused on developing new metal complex conjugates of Peptide Nucleic Acids (PNAs) as biosensors, and she investigated novel trace-less linkers for solid-phase synthesis of drug-like small molecules in collaboration with GlaxoSmithKline.

In 2004 she was awarded a Marie Curie EIF Individual Research Fellowship and appointed as Postdoctoral Research Assistant at the University of Cambridge with Professor Steven Ley, where she initiated a project focused on exploring the role of molecular diversity for drug discovery, with the design of natural product-like compounds as novel therapeutic agents.

In June 2006 she joined the School of Pharmacy, University College London (UCL) (London, UK) as a Senior Research Fellow funded by Cancer Research UK (CR UK), within the CR UK Protein-Protein Interactions Drug Discovery Research Group (unit director: Prof. David E. Thurston). As a co-PI of a CR UK Small Molecule Drug Discovery Initiative program she led the research aimed at discovering protein-protein inhibitors of transcriptional factors such as Hypoxia Inducible Factor 1 (HIF-1) and Signal Transducer and Activator of Transcription 3 (STAT3 ).

In January 2012 she took up the position at the Karolinska Institute as a junior PI at the Center for Advanced Cancer Therapies (ACT).

Research description

Dissecting and Manipulating Transcription Factors Networks

I focus on how protein-protein interactions regulate the transcription factors that control cell growth and differentiation. My ultimate goal is to help unravel the complex networks that regulate transcription and use this knowledge for therapeutic intervention in fields such as cancer, stem cell biology, regenerative medicine, inflammation and heart disease. To this end my research encompasses biochemistry, biophysics and structural biology to characterise these interactions, as well as chemical approaches to developmental chemical probes that target them.

Currently we are working on the MYC transcription factor, which can be considered to be one of the master regulator of cell growth, proliferation and differentiation as it governs numerous cellular processes including cell survival, apoptosis and metabolism. MYC, like many TFs, is an intrinsically disordered proteins and working on this system also allows us to address more general questions on how intrinsically disordered proteins (IDPs) exert their functions and how they can be targeted with small molecule, which have wider implications in many areas of biology. 

Research collaborations (in alphabetical order)

Dr Bruno Amati, European Institute of Oncology (IEO), Milan, Italy

Prof. Don Ayer, Huntsman Cancer Institute, University of Utah, USA

Dr Mark Bycroft, MRC LMB, Cambridge, UK

Prof. Martin Eilers, Theodor Boveri Institut, University of Würzburg, Germany

Prof. Gerard Evan, University of Cambridge, UK

Prof. Lars-Gunnar Larsson, Karolinska Institute, Sweden

 

 

Links

Publications

A New Way Forward in Cancer Drug Discovery: Inhibiting the SWI/SNF Chromatin Remodelling Complex
Zinzalla G
Chembiochem : a European journal of chemical biology 2016;17(8):677-82

Targeting MYC: is it getting any easier?
Zinzalla G
FUTURE MEDICINAL CHEMISTRY 2016;8(16):1899-1902

Paving the way to targeting HECT ubiquitin ligases
Zinzalla G
Future medicinal chemistry 2015;7(16):2107-11

Targeting protein-protein interactions (PPIs) of transcription factors: Challenges of intrinsically disordered proteins (IDPs) and regions (IDRs)
Sammak S, Zinzalla G
Progress in biophysics and molecular biology 2015;119(1):41-6

The SWI/SNF Subunit INI1 Contains an N-Terminal Winged Helix DNA Binding Domain that Is a Target for Mutations in Schwannomatosis
Allen Md, Freund Sm, Zinzalla G, Bycroft M
Structure (London, England : 1993) 2015;23(7):1344-9

Tetracycline analogues with a selective inhibitory effect on HIF-1 alpha
Bendiabdellah Y, Rahman Km, Uranchimeg B, Nahar Ks, Antonow D, Shoemaker Rh, et al
MEDCHEMCOMM 2014;5(7):923-926

Investigation of the protein alkylation sites of the STAT3:STAT3 inhibitor Stattic by mass spectrometry
Heidelberger S, Zinzalla G, Antonow D, Essex S, Basu Bp, Palmer J, et al
Bioorganic & medicinal chemistry letters 2013;23(16):4719-22

Observation of unphosphorylated STAT3 core protein binding to target dsDNA by PEMSA and X-ray crystallography
Nkansah E, Shah R, Collie Gw, Parkinson Gn, Palmer J, Rahman Km, et al
FEBS LETTERS 2013;587(7):833-9

Molecular Dynamics Studies of the STAT3 Homodimer:DNA Complex: Relationships between STAT3 Mutations and Protein-DNA Recognition
Husby J, Todd Ak, Haider Sm, Zinzalla G, Thurston De, Neidle S
JOURNAL OF CHEMICAL INFORMATION AND MODELING 2012;52(5):1179-92

Small-molecule inhibition of c-MYC:MAX leucine zipper formation is revealed by ion mobility mass spectrometry
Harvey Sr, Porrini M, Stachl C, Macmillan D, Zinzalla G, Barran Pe
Journal of the American Chemical Society 2012;134(47):19384-92

One-Pot Synthesis of Fused-Tetracyclic Scaffolds Employing a Lewis Acid Promoted Domino Reaction of Naphthoquinones
Bendiabdellah Y, Villanueva-margalef I, Misale A, Nahar Ks, Haque Mr, Thurston De, et al
SYNTHESIS-STUTTGART 2011;:2321-2333

A novel small-molecule inhibitor of IL-6 signalling
Zinzalla G, Haque Mr, Basu Bp, Anderson J, Kaye Sl, Haider S, et al
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 2010;20(23):7029-32

Facile nucleophilic substitution at the C3a tertiary carbon of the 3a-bromohexahydropyrrolo[2,3-b]indole scaffold
Villanueva-margalef I, Thurston De, Zinzalla G
ORGANIC & BIOMOLECULAR CHEMISTRY 2010;8(23):5294-303

Facile oxidation of electron-poor benzo[b]thiophenes to the corresponding sulfones with an aqueous solution of H2O2 and P2O5
Antonow D, Marrafa T, Dawood I, Ahmed T, Haque Mr, Thurston De, et al
CHEMICAL COMMUNICATIONS 2010;46(13):2289-91

Novel small-molecule inhibitors of Interleukin-6 (IL-6) signalling
Haque M, Zinzalla G, Basu Bp, Anderson J, Haider S, Hasan F, et al
EJC SUPPLEMENTS 2010;8(7):43-43

Total synthesis of YM-181741 for the preparation of natural product-like STAT3:STAT3 inhibitors
Misale A, Antonow D, Thurston De, Zinzalla G
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 2010;:-

Targeting protein-protein interactions for therapeutic intervention: a challenge for the future
Zinzalla G, Thurston De
FUTURE MEDICINAL CHEMISTRY 2009;1(1):65-93

Natural-Product-Like Spiroketals and Fused Bicyclic Acetals as Potential Therapeutic Agents for B-Cell Chronic Lymphocytic Leukaemia
Milroy Lg, Zinzalla G, Loiseau F, Qian Zz, Prencipe G, Pepper C, et al
CHEMMEDCHEM 2008;3(12):1922-35

Chemical variation of natural-product-like scaffolds: Design, synthesis, and biological activity of fused bicyclic acetal derivatives
Milroy Lg, Zinzalla G, Prencipe G, Michel P, Ley Sv, Gunaratnam M, et al
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 2007;46(14):2493-6

A new ferrocene conjugate of a tyrosine PNA monomer: synthesis and electrochemical properties (vol 689, pg 4791, 2004)
Baldoli C, Falciola L, Licandro E, Maiorana S, Mussini P, Ramani P, et al
JOURNAL OF ORGANOMETALLIC CHEMISTRY 2006;691(3):539-539

Chemical variation of natural product-like scaffolds: design and synthesis of spiroketal derivatives
Zinzalla G, Milroy Lg, Ley Sv
ORGANIC & BIOMOLECULAR CHEMISTRY 2006;4(10):1977-2002

A new ferrocene conjugate of a tyrosine PNA monomer: synthesis and electrochemical properties
Baldoli C, Falciola L, Licandro E, Maiorana S, Mussini P, Ramani P, et al
JOURNAL OF ORGANOMETALLIC CHEMISTRY 2004;689(25):4791-4802

A thymine-PNA monomer as new isocyanide component in the Ugi reaction: A direct entry to PNA dimers
Baldoli C, Giannini C, Licandro E, Maiorana S, Zinzalla G
SYNLETT 2004;:1044-1048

Polymer-supported haloarene chromium dicarbonyl isonitrile complexes: A study of their synthesis and reactivity
Baldoli C, Maiorana S, Licandro E, Casiraghi L, Zinzalla G, Seneci P, et al
JOURNAL OF COMBINATORIAL CHEMISTRY 2003;5(6):809-13

Synthesis of chiral chromium tricarbonyl labeled thymine PNA monomers via the Ugi reaction
Baldoli C, Maiorana S, Licandro E, Zinzalla G, Perdicchia D
ORGANIC LETTERS 2002;4(24):4341-4

Stereoselective hetero Diels-Alder reactions of chiral tricarbonyl (eta(6)-benzaldehyde)chromium complexes
Baldoli C, Maiorana S, Licandro E, Zinzalla G, Lanfranchi M, Tiripicchio A
TETRAHEDRON-ASYMMETRY 2001;12(15):2159-2167

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